PROJECT SUMMARY Incidence rates for a range of adverse child developmental conditions have increased in recent years in the US and elsewhere. There is emerging evidence and concern that exposure to environmental chemicals such as phenols, parabens, and others may contribute to this recent rise in developmental disorders. Additionally, disparities exist in both incidence rates of adverse health conditions and level of pollutant exposure. There are particularly high rates of a number of developmental conditions, as well as elevated exposures to phenols and parabens, in Puerto Rico. Environmental phenols and parabens disrupt endocrine function, induce oxidative stress, and cause other alterations that may result in reduced fetal or child growth, preterm birth, reproductive tract anomalies, neurodevelopmental delays, obesity, allergies/asthma, and other effects. While near- ubiquitous exposures to these chemicals have been documented among pregnant women, well-designed human studies are greatly needed to determine whether developmental impacts are related to early life in utero exposure. In addition, few studies have addressed the real life situation of considering multiple exposures and susceptibility factors individually and together. Our preliminary data show that pregnant women in Puerto Rico may have higher exposures to several of these chemicals than women in the US and elsewhere, significant associations between these chemicals and markers of hypothesized mechanistic pathways, and that certain modifiable behaviors, such as use of specific products during pregnancy, are associated with elevated chemical exposure and suggest effective intervention strategies may be possible. The proposed project is designed to fill these research gaps by leveraging an ongoing NIH-funded pregnancy cohort study in Puerto Rico (P42ES017198) that is building a rich dataset on environmental, clinical, social, demographic, behavioral, dietary and other factors among 1800 pregnant women. The proposed study will follow 600 children born into the cohort through the age of 4 years. Our specific aims are to 1) Investigate the association between prenatal exposure to environmental phenols and parabens, estimated via urinary biomarkers at multiple times during pregnancy, and pregnancy outcomes and child development (including preterm birth, measures of infant feeding, child growth, reproductive development, neurodevelopment, and lung function); 2) Provide evidence for biological mechanisms that may mediate the relationship between early life exposure to environmental phenols or parabens and fetal/child development, including endocrine disruption, inflammation, and oxidative stress; 3) Test effect modification of the relationship between phenols or parabens and fetal/child development by a range of susceptibility factors, including socioeconomic status, maternal stress, and preterm birth; and 4) develop and apply innovative statistical approaches to explore fetal/child development effects of early-life exposure to multi-pollutant mixtures when also incorporating air pollution data that will be collected in Project 1 of this Center, and biomarker data on phthalates and metals being measured as part of the parent study.